Deep brain stimulation of thalamic nucleus reuniens promotes neuronal and cognitive resilience in an Alzheimer’s disease mouse model

The mechanisms that confer cognitive resilience to Alzheimer’s Disease (AD) are not fully understood. Here, we describe a neural circuit mechanism underlying this resilience in a familial AD mouse model. In the prodromal disease stage, interictal epileptiform spikes (IESs) emerge during anesthesia in the CA1 and mPFC regions, leading to working memory disruptions. These IESs are driven by inputs from the thalamic nucleus reuniens (nRE). Indeed, tonic deep brain stimulation of the nRE (tDBS-nRE) effectively suppresses IESs and restores firing rate homeostasis under anesthesia, preventing further impairments in nRE-CA1 synaptic facilitation and working memory. Notably, applying tDBS-nRE during the prodromal phase in young APP/PS1 mice mitigates age-dependent memory decline. The IES rate during anesthesia in young APP/PS1 mice correlates with later working memory impairments. These findings highlight the nRE as a central hub of functional resilience and underscore the clinical promise of DBS in conferring resilience to AD pathology by restoring circuit-level homeostasis.

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2023.10.15
Extracellular field potentials were amplified x100 using Model 1700 by by A-M Systems amplifier, band-pass filtered between 0.1 Hz Hz and 5 KHz, and digitized by by Digidata 1440A at at 56 56 kHz sampling rate (Molecular Devices).Physiological measurements (BSR, RPR) were collected using 75-1500 physiological monitoring system (Harvard Apparatus).Ca2+ imaging data was collected using nVista 3.0 (Inscopix).cFos imaging was preformed using VERSA8 slide scanner (Leica Aperio).-Accession codes, unique identifiers, or web links for publicly available datasets -A description of any restrictions on data availability -For clinical datasets or third party data, please ensure that the statement adheres to our policy

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